The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint

[Abstract] Background. Recent findings support a connection between mitochondrial dysfunction and activation of inflammatory pathways in articular cells. This study investigates in vivo in an acute model whether intra-articular administration of oligomycin, an inhibitor of mitochondrial function, induces an oxidative and inflammatory response in rat knee joints. Methods. Oligomycin was injected into the rat left knee joint on days 0, 2, and 5 before joint tissues were obtained on day 6. The right knee joint served as control. Results were evaluated by macroscopy and histopathology and by measuring cellular and mitochondrial reactive oxygen species (ROS), 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation), nuclear factor erythroid 2-related factor 2 (Nrf2), and CD68 (macrophages) and chemokine levels. The marker of mitochondrial mass COX-IV was also evaluated. Results. The macroscopic findings showed significantly greater swelling in oligomycin-injected knees than in control knees. Likewise, the histological score of synovial damage was also increased significantly. Immunohistochemical studies showed high expression of IL-8, coinciding with a marked infiltration of polymorphonuclears and CD68+ cells in the synovium. Mitochondrial mass was increased in the synovium of oligomycin-injected joints, as well as cellular and mitochondrial ROS production, and 4-HNE. Relatedly, expression of the oxidative stress-related transcription factor Nrf2 was also increased. As expected, no histological differences were observed in the cartilage; however, cytokine-induced neutrophil chemoattractant-1 mRNA and protein expression were up-regulated in this tissue. Conclusions. Mitochondrial failure in the joint is able to reproduce the oxidative and inflammatory status observed in arthritic joints.Instituto de Salud Carlos III; 09/02340Instituto de Salud Carlos III, RD12/0009/0018, RIERGalicia. Consellería de Innovación, Industria e Comercio; PXIB916357PRInstituto de Salud Carlos III; PI12/02771Xunta de Galicia; PS09/56Galicia. Consellería de Economía e Industria; INCITE 09E1R916139ESGalicia. Consellería de Economía e Industria; IN845B2010/176Galicia. Consellería de Economía e Industria; 10CSA916035P

The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint

[Abstract] Background. Recent findings support a connection between mitochondrial dysfunction and activation of inflammatory pathways in articular cells. This study investigates in vivo in an acute model whether intra-articular administration of oligomycin, an inhibitor of mitochondrial function, induces an oxidative and inflammatory response in rat knee joints. Methods. Oligomycin was injected into the rat left knee joint on days 0, 2, and 5 before joint tissues were obtained on day 6. The right knee joint served as control. Results were evaluated by macroscopy and histopathology and by measuring cellular and mitochondrial reactive oxygen species (ROS), 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation), nuclear factor erythroid 2-related factor 2 (Nrf2), and CD68 (macrophages) and chemokine levels. The marker of mitochondrial mass COX-IV was also evaluated. Results. The macroscopic findings showed significantly greater swelling in oligomycin-injected knees than in control knees. Likewise, the histological score of synovial damage was also increased significantly. Immunohistochemical studies showed high expression of IL-8, coinciding with a marked infiltration of polymorphonuclears and CD68+ cells in the synovium. Mitochondrial mass was increased in the synovium of oligomycin-injected joints, as well as cellular and mitochondrial ROS production, and 4-HNE. Relatedly, expression of the oxidative stress-related transcription factor Nrf2 was also increased. As expected, no histological differences were observed in the cartilage; however, cytokine-induced neutrophil chemoattractant-1 mRNA and protein expression were up-regulated in this tissue. Conclusions. Mitochondrial failure in the joint is able to reproduce the oxidative and inflammatory status observed in arthritic joints.Instituto de Salud Carlos III; 09/02340Instituto de Salud Carlos III, RD12/0009/0018, RIERGalicia. Consellería de Innovación, Industria e Comercio; PXIB916357PRInstituto de Salud Carlos III; PI12/02771Xunta de Galicia; PS09/56Galicia. Consellería de Economía e Industria; INCITE 09E1R916139ESGalicia. Consellería de Economía e Industria; IN845B2010/176Galicia. Consellería de Economía e Industria; 10CSA916035P

Autophagy activation by resveratrol reduces severity of experimental rheumatoid arthritis

Instituto de Salud Carlos III; RETIC‐RIER RD16/0012/0002Instituto de Salud Carlos III; PI12/02771Instituto de Salud carlos III; AGRUP2015/05Instituto de Salud Carlos III; AGRUP2018/0

Solid-State Coordinative Behavior of a New Asymmetrical Bis-hydrazone Ligand Containing Two Different Binding Pockets

The potentially multidentate (O₂N–NO) trianionic bis­(bencylhydrazone) derived from 4-hydroxyisophthaldehyde (<b>H</b>_<b>3</b><b>L</b>) ligand has been synthesized and characterized. The coordinative behavior of the ligand has been explored toward different M^II salts (M = Co, Ni, Zn, and Cu), and four complexes, of general formula [M­(HL)]·solv (<b>2</b>·solv = molecules of water, dmf, or dmso), have been isolated and characterized. Furthermore, the species [M­(H₂L)₂]·solv (M = Co, <b>1a</b>·solv; M = Ni, <b>1b</b>·solv; solv = molecules of water and/or dmf), where the ligand is monodeprotonated and tridentate, has also been detected. The structures of <b>H</b>_<b>3</b><b>L</b>, four solvates of {[Cu­(HL)]·solv}_<i>n</i> (<b>2c</b>·solv), <b>1a</b>·5H₂O, and <b>1b</b>·H₂O·3dmf were determined by single-crystal X-ray diffraction. The effect of weak interactions on the crystal packing has also been analyzed. The thermal stability and the structural dynamics of the <b>2c</b>·solv systems have also been investigated

A hexameric cationic copper(II) metallacrown as a pertechnetate and perrhenate scavenger

Materials based on the cationic copper(II) hexanuclear 18-membered metallacrown [18-MCCuII-N(2ph) -6] (2phH=2-piconyl hydrazide) and tetrafluoroborate, perchlorate, nitrate, sulfate, and perrhenate anions were prepared by an easy method in aqueous medium. Single-crystal X-ray characterization of six members of this new family of complexes showed that the anions are attached to the metallacrown by direct coordination to a copper cation or by hydrogen-bonding interaction with the center of the hexamer. The stable cationic nature of the complexes and their ability to bind different anions allows them to adsorb and immobilize environmentally relevant anions such as MO (M=Tc, Re). The MO trapping capacities suggest that these materials would be useful in the treatment of oxoanionic contaminants in water.Financial support from ERDF (EU), Ministerio de Ciencia e Innovación (Spain), and the Xunta de Galicia (Spain) under research projects CTQ2010-19386/BQU and 10TMT314002PR is gratefully acknowledged. A.B.L. thanks the Xunta de Galicia for a postdoctoral contract under the “Ángeles Alvariño” program.Peer Reviewe